Xenon Encapsulation in Liposomes, Nanobubbles, and Microbubbles: Delivery Strategies, Preclinical Evidence, and Translational Barriers.

Xenon is an active noble gas with anesthetic, neuroprotective and organ-protective properties, but its therapeutic application remains limited by high cost, the need for specialized delivery systems, and the inefficiency of conventional inhalation administration. In this context, Xenon encapsulation into lipid-based nanocarriers, including liposomes and microbubbles, has emerged as a promising strategy to improve targeted delivery, reduce overall Xenon consumption, and enable stimulus-responsive release. This review summarizes current approaches to Xenon loading into liposomes and microbubbles, with emphasis on formulation principles, physicochemical characteristics, stability, acoustic behavior, and ultrasound-triggered release. We further analyze available evidence from preclinical animal models, particularly ischemic stroke, traumatic brain injury, and subarachnoid hemorrhage, where Xenon-loaded carriers have demonstrated the potential to reduce tissue injury and improve functional outcomes. Particular attention is given to the comparative advantages and limitations of liposomal and microbubble-based platforms, including the loading efficiency, circulation behavior, and translational feasibility. Overall, Xenon encapsulation technologies represent a promising direction for the development of localized and potentially more economical Xenon-based therapy. However, further standardization of carrier characterization, dosing strategies, and preclinical protocols is required before these systems can be reliably advanced toward clinical translation.